The long-term aims of this project are 1) to determine the impact of peripheral trigeminal nerve injury upon the development of monoaminergic projections and receptor populations in the CNS and 2) to assess the role of serotonin in establishing the anatomical and physiological characteristics of the trigeminal thalamocortical projection. Four experiments are proposed: 1. The normal development of monoaminergic innervation patterns will be correlated with the development of the whisker representation in the trigeminal system using immunocytochemistry, HPLC, high affinity uptake analysis and receptor binding autoradiography; 2. Potential changes in monoaminergic projections and receptor populations will be evaluated after neonatal destruction of a single row of vibrissa follicles, using methods listed above, to determine the role of competition between somatotopically organized afferents in the establishment of monoaminergic plexi and to obtain data which will reveal the degree to which CNS neuropil must be altered in order to affect the development of the monoaminergic systems; 3. The importance of an intact peripheral innervation in the development of trigeminal monoaminergic innervation will be evaluated after neonatal infraorbital nerve transection using the methods listed above. The massive neuropil reorganization after this lesion provides a complementary model to that outlined in Experiment 2; 4. Serotonin may regulate the elongation of axons and the establishment of axon terminals during development. Neonatal treatment with either p- chloroamphetamine or 5,7 dihydroxytrypramine will be used to destroy cortical serotonin projections and the morphology, distribution and bouton density of individual thalamocortical axons will be studied by the morphometric analysis of axons labeled by PHA-L. The role of monamines in sensory perception is suggested by psychotropic drug effects. Also, some psychotropic drugs ablate cortical serotoninergic projections. Thus, the effects of trigeminal injury upon monoamines and the results of serotonin depletion on thalamocortical development are important factors in the definition of injury sequelae in the trigeminal system.
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